Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis

نویسندگان

  • Joseph M. Carroll
  • M.Rosario Romero
  • Fiona M. Watt
چکیده

Integrin expression is normally confined to the basal layer of the epidermis, but when epidermal homeostasis is perturbed, the receptors are also expressed by suprabasal, differentiating keratinocytes. We have used the involucrin promoter to express functional human integrin subunits alpha 2, alpha 5, and beta 1 in the suprabasal epidermal layers of transgenic mice. In mice expressing alpha 5 or beta 1 alone or alpha 2 beta 1 or alpha 5 beta 1 heterodimers, there were hair and whisker abnormalities and a failure of eyelid fusion. In addition, mice expressing beta 1 alone or in combination with alpha 2 or alpha 5 exhibited epidermal hyper-proliferation, perturbed keratinocyte differentiation, and skin inflammation, all of which are features of a common human skin disease, psoriasis.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis.

In normal epidermis, beta1 integrin expression is confined to the basal layer, whereas in hyperproliferative epidermis, integrins are also expressed in the suprabasal layers. Transgenic mice in which integrins are expressed suprabasally via the involucrin promoter have a sporadic psoriatic phenotype; however, the mechanism by which integrins contribute to the pathogenesis of psoriasis is unknow...

متن کامل

Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1

Psoriasis is a complex human-specific disease characterized by perturbed keratinocyte proliferation and a pro-inflammatory environment in the skin. Porcine skin architecture and immunity are very similar to that in humans, rendering the pig a suitable animal model for studying the biology and treatment of psoriasis. Expression of integrins, which is normally confined to the basal layer of the e...

متن کامل

Suprabasal Dsg2 expression in transgenic mouse skin confers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes.

Desmoglein 2 (Dsg2), a component of the desmosomal cell-cell adhesion structure, has been linked to invasion and metastasis in squamous cell carcinomas. However, it is unknown whether--and if so how--Dsg2 contributes to the malignant phenotype of keratinocytes. In this study, we addressed the consequences of Dsg2 overexpression under control of the involucrin promoter (Inv-Dsg2) in the epidermi...

متن کامل

Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis.

In a series of transgenic mice, the human tissue collagenase gene was expressed in the suprabasal layer of the skin epidermis. Visually, the mice had dry and scaly skin which upon histological analysis revealed acanthosis, hyperkeratosis, and epidermal hyperplasia. At the ultrastructural level, intercellular granular materials were absent in the transgenic skin epidermis but contact was maintai...

متن کامل

Suprabasal desmoglein 3 expression in the epidermis of transgenic mice results in hyperproliferation and abnormal differentiation.

The desmoglein 1 (Dsg1) and desmocollin 1 (Dsc1) isoforms of the desmosomal cadherins are expressed in the suprabasal layers of epidermis, whereas Dsg3 and Dsc3 are more strongly expressed basally. This differential expression may have a function in epidermal morphogenesis and/or may regulate the proliferation and differentiation of keratinocytes. To test this hypothesis, we changed the express...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cell

دوره 83  شماره 

صفحات  -

تاریخ انتشار 1995